Mutational landscape of B-cell post-transplant lymphoproliferative disorders

作者：Menter Thomas; Juskevicius Darius; Alikian Mary; Steiger Juerg; Dirnhofer Stephan; Tzankov Alexandar^*; Naresh Kikkeri N^*

来源：British Journal of Haematology, 2017, 178(1): 48-56.

DOI：10.1111/bjh.14633

• diffuse large B-cell lymphomas
• post-transplant lymphoproliferative disorders
• Epstein-Barr virus
• TP53
• next generation sequencing

It is currently unclear whether post-transplant diffuse large B-cell lymphomas (PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA. Non-tumoural tissue was sequenced to exclude germline variants in cases where available. A control cohort of 76 IC-DLBCL was available for comparative analyses. In comparison to IC-DLBCLs, PT-DLBCL showed more frequent mutations of TP53 (P = 0.004), and absence of ATM and B2M mutations (P = 0.004 and P = 0.016, respectively). In comparison to IC-DLBCLs, Epstein-Barr virus (EBV)+ PT-DLBCL had fewer mutated genes (P = 0.007) and particularly fewer mutations in nuclear factor-kappa B pathway-related genes (P = 0.044). TP53 mutations were more frequent in EBV PT-DLBCL as compared to IC-DLBCL (P = 0.001). Germinal centre B cell (GCB) subtype of PT-DLBCL had fewer mutations and mutated genes than GCB-IC-DLBCLs (P = 0.048 and 0.04 respectively). Polymorphic PTLD displayed fewer mutations as compared to PT-DLBCL (P = 0.001). PT-DLBCL differs from IC-DLBCL with respect to mutations in genes related to DNA damage control and immune-surveillance, and EBV association is likely to have a bearing on the mutational pattern.

• 出版日期2017-7